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Use of Topical Analgesics in Treating Neuropathic and Musculoskeletal Pain All Rights Reserved

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Use of Topical Analgesics in Treating Neuropathic and Musculoskeletal Pain All Rights Reserved PRINTER-FRIENDLY VERSION AVAILABLE AT PAINMEDICINENEWS.COM Use of Topical Analgesics in Treating Neuropathic and Musculoskeletal Pain All rights reserved. Reproduction in whole or in part without permission is prohibited. WILLIAM ZEMPSKY Copyright, MD © 2013 McMahon Publishing Group unless otherwise noted. Head, Divison of Pain and Palliative Medicine Connecticut Children’s Medical Center Professor of Pediatrics University of Connecticut School of Medicine Storrs, Connecticut Disclosure: Dr. Zempsky serves on the Scientific Advisory Board of Vapogenicx, Inc. opical administration of anesthetics and analgesics can allow for the efficient, painless delivery of medications that may reduce systemic side effects Tassociated with the medication while providing clinical advantages over injected or oral administration for the same clinical situation. Topical administration of nonsteroidal anti-inflammatory drugs (NSAIDs), lidocaine, capsaicin, and other agents is useful for a range of conditions including acute and chronic musculoskeletal pain. Background substances, which typically include anesthetics. Topi- Topical medications target the site of application and cal medications must traverse the stratum corneum ideally produce effective drug concentrations locally to reach their site of action, which may be the periph- with minimal systemic absorption. Topical anesthetics eral transducing terminals of cutaneous sensory fibers and analgesics target the peripheral nerves and soft tis- located in the dermis and epidermis,4 or the local soft sue at that site.1 A number of topical medications are tissues including synovial fluid, synovial tissue, and car- beneficial for chronic musculoskeletal pain. In contrast, tilaginous structures.5 transdermal medications do not have to be applied over Three delivery methods have been used to bypass an involved site and attempt to reach systemic drug the stratum corneum barrier.6 concentrations to achieve therapeutic results.2 This 1. Injection of local anesthetics or other medications, review will focus on topical medications (Table). usually via a small-gauge hypodermic syringe, is the Benefits of topical drug delivery include the poten- oldest of the methodologies. tial for local therapeutic drug levels with reduced side 2. Passive diffusion from creams, gels, or patches com- effects, painless drug delivery, improved patient adher- prises the second general class of methodologies. ence and acceptance, ease of dose termination, avoid- Passive diffusion of topical agents require that they ance of first-pass metabolism, and direct access to the have a molecular weight under 500 DA, with a hydro- target site. phobic component to allow it to transverse the stra- The skin is a barrier to drug delivery, its primary role tum corneum but also some hydrophilic features to being to prevent the ingress or egress of compounds penetrate the epidermis.7 across it.3 The stratum corneum, the upper most layer 3. Active drug delivery methods that enhance the rate of the skin, is a thin layer of cornified nonviable kera- of drug passage through the skin and shorten the tinocytes that is an effective barrier to water-soluble time to onset of action. There are a diverse group of INDEPENDENTLY DEVELOPED BY MCMAHON PUBLISHING PAIN MEDICINE NEWS • SEPTEMBER 2013 1 of neuropathic pain conditions, such as post-thoracot- Table. Common Topical Anesthetics omy pain, complex regional pain syndrome, and post- and Analgesics for Chronic Pain amputation pain.12 The lidocaine patch also is effective Brand or Other for musculoskeletal conditions. The 5% lidocaine patch Drug Names Use Formulation is effective in adults with osteoarthritis (OA)13,14 lower back pain.15,16 It also has shown efficacy for myofascial Arnica MSK pain Gel, cream pain syndrome.17 Capsaicin Zostrix, Qutenza, Neuro pathic Patch, gel, The lack of significant side effects makes topical 5% others pain, MSK pain cream lidocaine an appropriate option for any focal neuropathic Lidocaine Lidoderm Neuro pathic Patch pain with allodynia or hyperalgesia.18 The patch must be pain, MSK pain All rights reserved. Reproduction in whole or placedin part at without the site of permission pain in order isto prohibited.be effective. Menthol and Many MSK pain Oinment, Although it has not been studied specifically in chil- methyl salicylates liniment Copyright © 2013 McMahon Publishingdren, we Group have used unless the 5%otherwise lidocaine noted.patch successfully cream in many of the conditions described above, especially Topical NSAIDs Flector, Voltaren, MSK pain Patch, gel, low back pain and focal neuropathic pains. Lidocaine Pennsaid, others cream absorption in adult usage amounts to only 3% to 5 % of NSAID, nonsteroidal anti-inflammatory drug; the total dose available in the patch and systemic levels MSK, musculoskeletal do not increase with daily use. Systemic toxicity in adults is not considered a significant risk.19,20 For children under technologies that facilitate the drug delivery process. 50 kg, we limit the treatment to 1 to 2 patches for 12 These include heat-enhanced diffusion, iontophore- hours per day to ensure safety. For children weighing sis, sonophoresis, laser-assisted transdermal pas- more than 50 kg the adult dose of 3 patches for 12 sage, or pressurized gas delivery of powdered drug hours per day is recommended. Often, 7 to 10 days of particles.6 Microporation, a newer technology, uses treatment is necessary before efficacy is noted. Side tiny microneedles to penetrate the stratum corneum effects usually are limited to redness or other signs of and are directly placed within the epidermis. skin irritation. Topical as well as transdermal drug delivery is a rap- idly expanding field. Most of the drugs and technolo- NSAIDS gies used for procedural topical anesthesia have been Topical NSAIDS can provide local relief without the well studied; however, this is not universally the case risks of an orally or parenterally delivered NSAID. Pri- for topical medications used for musculoskeletal pain, marily, they have been evaluated for OA and acute mus- which will be discussed in this review. Additionally, most culoskeletal injury. These drugs are applied over the of these topical agents have been studied exclusively injured or painful body part and penetrate into the sub- in adults. The extrapolation of use of the these agents cutaneous tissues, musculature, and tendons, where in children seems reasonable given several factors, they exert their therapeutic action.21 the pharmacodynamic response to most medications After administration of topical NSAIDs, peak plasma including local anesthetics, opioids, and NSAIDs are concentrations are 0.2% to 8% of concentrations substantially mature by the age of 2 years, the degree achieved with appropriate oral dosing.22 However, lev- of systemic absorption of these topical medications is els of NSAID in the meniscus and cartilaginous struc- low, and the local skin effects are, for the most part, tures as well as in muscular tissues are 4 to 7 times minimal and short-lived.8 greater after topical administration than oral admin- istration.5,23 Concentrations in the tendon sheath are Topical Medications for Treatment of several hundred times greater than plasma concentra- Musculoskeletal Pain tion after topical administration. Length of time to peak LIDOCAINE concentration (Cmax) is about 10 times longer in topi- Although indicated for the treatment of posther- cally rather than orally administered NSAIDs with Cmax petic neuralgia (PHN) in the United States, lidocaine 5% for topical preparations ranging from 2.2 to 23 hours.22 topical anesthetic patch (Lidoderm, Endo) has gained Unlike orally administered NSAIDs, topical NSAIDs usage in a variety of neuropathic and musculoskeletal have not been associated with increased risk for bleed- clinical conditions. The 5% lidocaine patch is composed ing, and the risk for any gastrointestinal side effects for of an adhesive material containing lidocaine, which topical administration is considerably lower.5 Adverse is applied to a nonwoven polyester felt backing that events with topical NSAIDs are predominately local allows for slow medication release. The patch provides cutaneous reactions. Photosensitivity is a rare adverse analgesic action, reducing pain with some decrease in reaction to topical NSAIDs.5 Although there a fewer sensory function but without the complete loss of sen- comparative trials, in general, topical NSAIDs appear as sation; thus, it is not effective for procedural pain.9, 10 effective and have a better safety profile in adults than The size of the patch is 10-14 cm.11 oral NSAIDs, although onset of action is slower.22,24 In addition to treatment of PHN, the 5% lido- There are a variety of topical NSAID preparations caine patch has been used with efficacy in a variety including creams, gels, patches, and plasters. NSAIDS 2 INDEPENDENTLY DEVELOPED BY MCMAHON PUBLISHING delivered topically include diclofenac, ketoprofen, and Use of capsaicin in pediatrics is limited to case ibuprofen. Superiority of topical NSAIDs compared reports. Given the rare incidence of systemic side with placebo has been demonstrated for both diclof- effects, use of capsaicin for chronic pain in children and enac (Flector Patch, Pfizer) and ketoprofen patches adolescents could be considered and will be limited by (various)for acute musculoskeletal conditions.25 Based tolerance to the application. on a large meta-analysis, ketoprofen may be the most Other counter-irritants such as methyl
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